U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Malignant hyperthermia, susceptibility to, 6

MedGen UID:
356150
Concept ID:
C1866076
Finding
Synonyms: Malignant hyperpyrexia susceptibility type 6; Malignant hyperthermia susceptibility type 6; MHS6-Related Malignant Hyperthermia Susceptibility
 
Monarch Initiative: MONDO:0011164
OMIM®: 601888

Disease characteristics

Excerpted from the GeneReview: Malignant Hyperthermia Susceptibility
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. [from GeneReviews]
Authors:
Henry Rosenberg  |  Nyamkhishig Sambuughin  |  Sheila Riazi, et. al.   view full author information

Additional descriptions

From OMIM
Malignant hyperthermia (MH) is a life threatening disorder triggered in susceptible individuals on exposure to commonly used inhalational anaesthetics, e.g., halothane and the depolarizing muscle relaxant suxamethonium (succinyl choline) (summary by Robinson et al., 1997) For a phenotypic description and a discussion of genetic heterogeneity of susceptibility to malignant hyperthermia, see MHS1 (145600).  http://www.omim.org/entry/601888
From MedlinePlus Genetics
While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility.

Affected individuals may be at increased risk for "awake" malignant hyperthermia, in which the severe reaction occurs in response to physical activity, often while sick, rather than in reaction to exposure to a triggering drug.

People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). Malignant hyperthermia may not occur every time anesthesia is used. Many individuals who develop a severe reaction have previously been exposed to a triggering drug and not had a reaction.

Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, either given alone or in combination with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk of malignant hyperthermia may experience a rapid increase in heart rate and body temperature (hyperthermia), abnormally fast breathing, muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Without prompt treatment and cessation of the drugs, the body's reaction can cause multiple organs to be unable to function, including the heart (cardiac arrest) and kidneys (renal failure), and it can cause a blood clotting abnormality called disseminated intravascular coagulation. These complications may be life-threatening. (In medicine, the term malignant refers to conditions that are dangerous to one's health.)  https://medlineplus.gov/genetics/condition/malignant-hyperthermia

Professional guidelines

PubMed

Haverfield EV, Esplin ED, Aguilar SJ, Hatchell KE, Ormond KE, Hanson-Kahn A, Atwal PS, Macklin-Mantia S, Hines S, Sak CW, Tucker S, Bleyl SB, Hulick PJ, Gordon OK, Velsher L, Gu JYJ, Weissman SM, Kruisselbrink T, Abel C, Kettles M, Slavotinek A, Mendelsohn BA, Green RC, Aradhya S, Nussbaum RL
BMC Med 2021 Aug 18;19(1):199. doi: 10.1186/s12916-021-01999-2. PMID: 34404389Free PMC Article
Litman RS, Smith VI, Larach MG, Mayes L, Shukry M, Theroux MC, Watt S, Wong CA
Anesth Analg 2019 Apr;128(4):652-659. doi: 10.1213/ANE.0000000000004039. PMID: 30768455
Curtis S
AANA J 1996 Dec;64(6):557-62. PMID: 9204791

Curated

Orphanet Emergency Guidelines: Malignant hyperthermia

Recent clinical studies

Etiology

White R, Schiemann AH, Burling SM, Bjorksten A, Bulger T, Gillies R, Hopkins PM, Kamsteeg EJ, Machon RG, Massey S, Miller D, Perry M, Snoeck MMJ, Stephens J, Street N, van den Bersselaar LR, Stowell KM
Br J Anaesth 2022 Dec;129(6):879-888. Epub 2022 Oct 6 doi: 10.1016/j.bja.2022.08.029. PMID: 36208971
van den Bersselaar LR, Hellblom A, Gashi M, Kamsteeg EJ, Voermans NC, Jungbluth H, de Puydt J, Heytens L, Riazi S, Snoeck MMJ
Anesthesiology 2022 Jun 1;136(6):940-953. doi: 10.1097/ALN.0000000000004199. PMID: 35285867
Gonzalez A, Girard T, Dell-Kuster S, Urwyler A, Bandschapp O
Eur J Anaesthesiol 2021 Jul 1;38(7):751-757. doi: 10.1097/EJA.0000000000001399. PMID: 33259453
Landau ME, Kenney K, Deuster P, Campbell W
J Clin Neuromuscul Dis 2012 Mar;13(3):122-36. doi: 10.1097/CND.0b013e31822721ca. PMID: 22538307
Miranda AD, Donovan LA, Schuster LL, Gerber DR
Am J Crit Care 1997 Sep;6(5):368-74; quiz 375-6. PMID: 9283674

Diagnosis

Rodrigues G, Andrade PV, Santos JMD, Castro I, Amaral JLGD, Silva HCAD
Braz J Anesthesiol 2023 Mar-Apr;73(2):138-144. Epub 2022 Feb 2 doi: 10.1016/j.bjane.2021.10.021. PMID: 35121058Free PMC Article
Biesecker LG, Dirksen RT, Girard T, Hopkins PM, Riazi S, Rosenberg H, Stowell K, Weber J
Anesthesiology 2020 Dec 1;133(6):1277-1282. doi: 10.1097/ALN.0000000000003547. PMID: 32898259Free PMC Article
Correia AC, Silva PC, da Silva BA
Rev Bras Anestesiol 2012 Nov-Dec;62(6):820-37. doi: 10.1016/S0034-7094(12)70182-4. PMID: 23176990
Brandom BW
Curr Opin Anaesthesiol 2009 Dec;22(6):744-7. doi: 10.1097/ACO.0b013e328332a45b. PMID: 19812484
Rusyniak DE, Sprague JE
Med Clin North Am 2005 Nov;89(6):1277-96. doi: 10.1016/j.mcna.2005.06.002. PMID: 16227063

Therapy

Ramani S, Park S
J Mol Med (Berl) 2021 Jun;99(6):771-784. Epub 2021 Mar 16 doi: 10.1007/s00109-021-02048-4. PMID: 33728476
Litman RS, Smith VI, Larach MG, Mayes L, Shukry M, Theroux MC, Watt S, Wong CA
Anesth Analg 2019 Apr;128(4):652-659. doi: 10.1213/ANE.0000000000004039. PMID: 30768455
Butala B, Brandom B
Can J Anaesth 2017 Apr;64(4):396-401. Epub 2017 Jan 6 doi: 10.1007/s12630-017-0815-2. PMID: 28063098
Metterlein T, Zink W, Kranke E, Haneya A, Graf B, Kranke P
J Thorac Cardiovasc Surg 2011 Jun;141(6):1488-95. Epub 2011 Mar 3 doi: 10.1016/j.jtcvs.2011.01.034. PMID: 21376345
Rusyniak DE, Sprague JE
Med Clin North Am 2005 Nov;89(6):1277-96. doi: 10.1016/j.mcna.2005.06.002. PMID: 16227063

Prognosis

Hoppe K, Jurkat-Rott K, Kranepuhl S, Wearing S, Heiderich S, Merlak S, Klingler W
Sci Rep 2021 Feb 9;11(1):3445. doi: 10.1038/s41598-021-82024-7. PMID: 33564012Free PMC Article
Butala B, Brandom B
Can J Anaesth 2017 Apr;64(4):396-401. Epub 2017 Jan 6 doi: 10.1007/s12630-017-0815-2. PMID: 28063098
Riazi S, Larach MG, Hu C, Wijeysundera D, Massey C, Kraeva N
Anesth Analg 2014 Feb;118(2):381-387. doi: 10.1213/ANE.0b013e3182937d8b. PMID: 23842196
Landau ME, Kenney K, Deuster P, Campbell W
J Clin Neuromuscul Dis 2012 Mar;13(3):122-36. doi: 10.1097/CND.0b013e31822721ca. PMID: 22538307
Metterlein T, Zink W, Kranke E, Haneya A, Graf B, Kranke P
J Thorac Cardiovasc Surg 2011 Jun;141(6):1488-95. Epub 2011 Mar 3 doi: 10.1016/j.jtcvs.2011.01.034. PMID: 21376345

Clinical prediction guides

Rodrigues G, Andrade PV, Santos JMD, Castro I, Amaral JLGD, Silva HCAD
Braz J Anesthesiol 2023 Mar-Apr;73(2):138-144. Epub 2022 Feb 2 doi: 10.1016/j.bjane.2021.10.021. PMID: 35121058Free PMC Article
van den Bersselaar LR, Hellblom A, Gashi M, Kamsteeg EJ, Voermans NC, Jungbluth H, de Puydt J, Heytens L, Riazi S, Snoeck MMJ
Anesthesiology 2022 Jun 1;136(6):940-953. doi: 10.1097/ALN.0000000000004199. PMID: 35285867
Gonzalez A, Girard T, Dell-Kuster S, Urwyler A, Bandschapp O
Eur J Anaesthesiol 2021 Jul 1;38(7):751-757. doi: 10.1097/EJA.0000000000001399. PMID: 33259453
Ibarra Moreno CA, Hu S, Kraeva N, Schuster F, Johannsen S, Rueffert H, Klingler W, Heytens L, Riazi S
Anesthesiology 2019 Nov;131(5):983-991. doi: 10.1097/ALN.0000000000002813. PMID: 31206373Free PMC Article
Brandom BW
Curr Opin Anaesthesiol 2009 Dec;22(6):744-7. doi: 10.1097/ACO.0b013e328332a45b. PMID: 19812484

Recent systematic reviews

Metterlein T, Zink W, Kranke E, Haneya A, Graf B, Kranke P
J Thorac Cardiovasc Surg 2011 Jun;141(6):1488-95. Epub 2011 Mar 3 doi: 10.1016/j.jtcvs.2011.01.034. PMID: 21376345

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...